International Perspectives on Substantiating the Efficacy of Herbal Dietary Supplements and Herbal Medicines Through Evidence on Traditional Use

The efficacy of botanicals in medicines can be substantiated with evidence on traditional use, whereas in foodstuffs, this is often not possible. In Europe, for example, the evaluation and subsequent authorization of health claims on herbal dietary supplements (HDS) have been put on hold by the European Commission. This study aims to analyze the role of evidence on traditional use in international legal frameworks of foods and pharmaceuticals. Both legal sources as well as scientific studies offering insights into these regulatory frameworks were included into the analysis. The international approach toward evidence on traditional use for substantiating efficacy of botanicals varies highly. For herbal medicines, substantiating efficacy with evidence on traditional use is possible in all studied jurisdictions, except for Japan and the United States. HDS efficacy can only be substantiated with evidence on traditional use in India and New Zealand, although the enforcing authorities do not describe which data are required. Australia and Canada regulate botanicals in a separate “borderline” category from foods and pharmaceuticals. Both jurisdictions allow for substantiating efficacy with evidence on traditional use. This study's second objective was to assess the applicability of the international approaches in the European legal framework, in light of the ongoing political debate regarding the use of traditional evidence. Implementation of the analyzed international approaches would require major revisions of the current European legal framework. This review of international approaches might, however, aid in deciding upon future approaches for substantiating health claims with evidence on traditional use.     

Effect of bioprocessing of wheat bran in wholemeal wheat breads on the colonic SCFA production in vitro and postprandial plasma concentrations in men

The health benefits of whole grain consumption can be partly attributed to the inclusion of the bran or outer-layers of the grain rich in dietary fibre. Fibre is fermented in the colon, leading to the production of beneficial metabolites, such as short-chain fatty acids (SCFA). The effect of five different types of bread on the SCFA production was studied in an in vitro model of human colon. Additionally, the postprandial effects of two selected breads on the SCFA plasma concentrations were investigated in men. A higher in vitro production of butyrate was induced by wholemeal wheat bread with bioprocessed bran than by native bran. The increase in butyrate seemed to be in exchange for propionate, whilst the total SCFA production remained similar. However, differences between the two breads in the postprandial butyrate concentrations could not be detected in peripheral blood of men, probably due to an effective utilisation by colonocytes.     

Patent Information User Groups in Europe join together: Foundation of the Confederacy of European Patent Information User Groups (CEPIUG)

The Confederacy of European Patent Information User Groups (CEPIUG) was founded in 2008 to promote the sharing of experiences and expertise in patent searching across Europe.CEPIUG currently comprises patent information user groups of seven different European countries and is, of course, open to new members. Besides the exchange of information, CEPIUG also seeks to promote the coordination of European efforts in the fields of education and training of new entrants into the profession of patent searching, as well as trying to identify a suitable certification scheme for patent information professionals.     

Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms

In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress–induced GC resistance in human macrophage-like cells. Cells were pre-treated with H₂O₂ (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2′,7′-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect.     

The Minor Structural Difference between the Antioxidants Quercetin and 4′O-Methylquercetin Has a Major Impact on Their Selective Thiol Toxicity

Antioxidants act as intermediates by picking up the high unselective reactivity of radicals and transferring it to other molecules. In this process the reactivity is reduced and becomes selective. This channeling of the reactivity can cause selective toxicity. The antioxidant quercetin is known to channel the reactivity towards thiol groups. The present study compares the thiol reactivity of quercetin with that of 4′O-methylquercetin (tamarixetin) towards creatine kinase (CK), a vital protein that contains a critical thiol moiety. Our results showed that oxidized quercetin and oxidized tamarixetin both adduct CK, which then loses its enzymatic function. Ascorbate, an important representative of the antioxidant network, is able to prevent adduction to and thus the inhibition of the enzyme by tamarixetin but not by quercetin. Apparently, tamarixetin is less thiol toxic than quercetin, because—rather than adduction to CK—tamarixetin quinone prefers to pass reactivity to the antioxidant network, i.e., to ascorbate. The findings exemplify that radical scavenging flavonoids pick up the reactivity of radicals and act as a pivot in directing the way the reactivity is channeled. A mere minor structural difference of only one methyl moiety between quercetin and tamarixetin appears to have a high impact on the selective, thiol toxicity.     

The potential of flavonoids in the treatment of non-alcoholic fatty liver disease

The contemporary pathophysiological model of non-alcoholic fatty liver disease (NAFLD) comprises multiple parallel pathways with a dynamic cross talk that cumulate in steatosis and inflammation, and ultimately fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. So far, no pharmacological treatment has been approved. A major impediment of drugs, in general, is that they are intended to act on one single target in the pathology of a disease. However, the multitude of pathways involved in the pathogenesis of NAFLD underpins the need for treatments that address these various pathways. Interestingly, flavonoids have been found to have positive effects on lipid metabolism, insulin resistance, inflammation, and oxidative stress, the most important pathophysiological pathways in NAFLD. This puts flavonoids in the spotlight for the treatment of NAFLD and prompted us to review the existing evidence for the use of these food-derived compounds in the treatment of NAFLD.     

The anti-inflammatory effect of lycopene complements the antioxidant action of ascorbic acid and α-tocopherol

Tomato foods contain bioactive compounds, such as lycopene, ascorbic acid and α-tocopherol, which are assumed to show synergistic effects. The aim of the study was to investigate this presumed synergy. The effect on lipid peroxidation and inflammation was assessed. Lipid peroxidation was effectively inhibited by combinations of the compounds compared to the single compounds. Synergy between the combination of ascorbic acid and α-tocopherol was confirmed. Lycopene on its own effectively reduced inflammation by inhibiting the release of TNF-α and stimulating IL-10 production. The combination of lycopene, ascorbic acid and α-tocopherol tended to display a synergistic interaction on IL-10 production. Our observations highlight that lycopene mitigates inflammation, whereas ascorbic acid and α-tocopherol efficiently protect against lipid peroxidation. Both activities are complementary since they diminish the process of inflammation differently on different levels. In relation to health, this is an added value of fruit and vegetables such as tomato products that contain complementary bio-active compounds.     

Nutrition and Health – Transforming Research Traditions

In this contribution, we show that current scientific methodologies used in nutrition science and by regulatory agencies, such as the randomized control trial, limit our understanding of nutrition and health as they are to crude to capture the subtle pleiotropic nature of most nutrients. Thereby, regulatory agencies such as the European Food Safety Authority curb the development of scientific knowledge and industrial innovations within the nutritional field. In order to develop insights into the health impact of certain food and food-components, we need to realize that health is adaptation set within a homeostatic range. Increased performance of health, i.e., the maximum stimulation of health, typically seems 30–60% greater than the control group, with a width of no more than about a factor of ten, clarifying the difficulty of documenting responses of food-endogenous components within the homeostatic range of healthy people. A strategy to record subtle responses of food components is the summation of procentual effects of relevant health outcomes. We illustrate this approach with the action of flavanols on vascular health, specifically endothelial function.